Complex regional pain syndrome

The term "complex regional pain syndrome" (CRPS) refers to a syndrome that manifests itself as severe chronic pain in the limb in combination with local autonomic disorders and trophic disorders, which usually occurs after various peripheral injuries. The symptoms of complex regional pain syndrome are familiar to almost every doctor, but at the same time, the issues of terminology, classification, pathogenesis and treatment of this syndrome remain largely controversial.

In 1855, N.I. Pirogov described intense burning pain in the extremities, accompanied by vegetative and trophic disorders, occurring in soldiers some time after being wounded. He called these disorders "posttraumatic hyperesthesia". Ten years later, S. Mitchell and co-authors (Mitchell S., Morehouse G., Keen W.) described a similar clinical picture in soldiers who suffered in the American Civil War. S. Mitchell initially designated these conditions as "erythromelalgia", and then, in 1867, proposed the term "causalgia". In 1900, P.G. Sudek described similar manifestations in combination with osteoporosis and called them "dystrophy". Later, different authors described similar clinical conditions, invariably offering their own terms ("acute bone atrophy", "algoneurodystrophy", "acute trophic neurosis", "posttraumatic osteoporosis", "posttraumatic sympathalgia", etc.). In 1947, O. Steinbrocker described the shoulder-hand syndrome (pain, swelling, trophic disorders in the arm that occur after myocardial infarction, stroke, trauma and inflammatory diseases). In the same year, Evans (Evans J.) proposed the term "reflex sympathetic dystrophy", which until recently was generally accepted. In 1994, a new term was proposed to designate local pain syndromes combined with vegetative and trophic disorders - "complex regional pain syndrome".

Classification of complex regional pain syndrome

There are 2 types of complex regional pain syndrome. In case of damages not accompanied by damage to peripheral nerves, CRPS type I is formed. CRPS type II is diagnosed when the syndrome develops after damage to a peripheral nerve and is considered as a variant of neuropathic pain.

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Causes and pathogenesis of complex regional pain syndrome

The causes of complex regional pain syndrome type I can be injuries to the soft tissues of the limb, fractures, dislocations, sprains, fasciitis, bursitis, ligamentitis, thrombosis of veins and arteries, vasculitis, herpes infection. CRPS type II develops with damage to nerves due to compression, with tunnel syndromes, radiculopathy, plexopathy, etc.

The pathogenesis of complex regional pain syndrome is poorly understood. The possible role of aberrant regeneration between afferent (sensory) and efferent (autonomic) fibers is discussed in the origin of complex regional pain syndrome type II. It is postulated that prolonged pain can be fixed in memory, causing higher sensitivity to repeated pain stimuli. There is a point of view that areas of nerve damage become ectopic pacemakers with a sharply increased number of alpha-adrenoreceptors, which are excited spontaneously and under the action of circulating or released from sympathetic norepinephrine. According to another concept, in complex regional pain syndrome, activation of spinal neurons of a wide range, participating in the transmission of nociceptive information, is of particular importance. It is believed that after injury, intense excitation of these neurons occurs, leading to their sensitization. Subsequently, even weak afferent stimuli, acting on these neurons, cause a powerful nociceptive flow.

Due to microcirculation disorders leading to hypoxia, acidosis and accumulation of acidic metabolic products in the blood, there is an increased breakdown of phosphorus-calcium compounds of the bone with the development of osteoporosis. "Spotted" osteoporosis, usually observed in the early stages of the disease, is associated with the dominance of lacunar bone resorption processes. An important factor in the development of osteoporosis is immobilization. In some cases, it is caused by severe pain, in others - associated with the underlying disease (for example, paresis or plegia after a stroke) or therapeutic manipulations (immobilization after fractures). In all cases, a decrease in physical activity, prolonged immobilization lead to bone demineralization and the development of osteoporosis.

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Symptoms of complex regional pain syndrome

Women predominate among patients (4:1). The disease can occur at almost any age (from 4 to 80 years). CRPS on the lower extremities is noted in 58%, on the upper extremities - in 42% of cases. Involvement of several zones is observed in 69% of patients. Cases of complex regional pain syndrome on the face have been described.

The clinical manifestations of complex regional pain syndrome of all types are identical and consist of 3 groups of symptoms: pain, autonomic vaso- and sudomotor disorders, dystrophic changes in the skin, subcutaneous tissue, muscles, ligaments, bones.

• Spontaneous intense burning, stabbing, pulsating pains are typical for complex regional pain syndrome. The phenomenon of allodynia is quite typical. As a rule, the pain zone goes beyond the innervation of any nerve. Often, the intensity of pain greatly exceeds the severity of the injury. Increased pain is noted with emotional stress, movement.
• Vegetative disorders in complex regional pain syndrome include vaso- and sudomotor disorders. The former include edema, the severity of which may vary, as well as disorders of peripheral circulation (vasoconstrictor and vasodilatation reactions) and skin temperature, changes in skin color. Sudomotor disorders are manifested by symptoms of local increased (hyperhidrosis) or decreased sweating (hypohidrosis).
• Dystrophic changes in complex regional pain syndrome can affect almost all tissues of the limb. Decreased skin elasticity, hyperkeratosis, changes in hair (local hypertrichosis) and nail growth, atrophy of the subcutaneous tissue and muscles, muscle contractures, and joint stiffness are noted. Demineralization of bones and the development of osteoporosis are characteristic of complex regional pain syndrome. CRPS type I is characterized by constant pain in a certain part of the limb after an injury that does not affect large nerve trunks. Pain is usually observed in the distal part of the limb adjacent to the injured area, as well as in the knee and hip, in the I-II fingers of the hand or foot. Burning constant pain, as a rule, occurs several weeks after the initial injury, intensifies with movement, skin stimulation, and stress.

Stages of development of complex regional pain syndrome type I

Stage	Clinical characteristics
1 (0-3 months)	Burning pain and distal limb swelling. The limb is warm, swollen and painful, especially in the joint area. Local sweating and hair growth increase. A light touch can cause pain (applause) that persists after the impact has stopped. The joints become stiff, pain is present with both active and passive movements in the joint
II (after 3-6 months)	The skin becomes thin, shiny and cold. All other symptoms of stage 1 persist and intensify.
III (6-12 months)	The skin becomes atrophic and dry. Muscle contractures with deformation of the hands and feet

CRPS type II is characterized by burning pain, allodynia, and hyperpathy in the corresponding hand or foot. Pain usually occurs immediately after the nerve is injured, but may also appear several months after the injury. Initially, spontaneous pain is localized in the innervation zone of the damaged nerve, and then it can cover larger areas.

Main manifestations of complex regional pain syndrome type II

Sign	Description
Characteristics of pain	Constant burning, aggravated by light touch, stress and emotions, changes in external temperature or movements in the affected limb, visual and auditory stimuli (bright light, sudden loud sound). Allodynia/hyperalgesia is not limited to the innervation zone of the damaged nerve
Other manifestations	Changes in skin temperature and color. Presence of edema. Impaired motor functions

Additional research

Thermography can detect changes in skin temperature on the affected limb, reflecting peripheral vaso- and sudomotor disorders. X-ray examination of bones is mandatory for all patients with complex regional pain syndrome. In the early stages of the disease, "spotted" periarticular osteoporosis is detected, as the disease progresses, it becomes diffuse.

Treatment of complex regional pain syndrome

Therapy for complex regional pain syndrome is aimed at eliminating pain and normalizing vegetative sympathetic functions. Treatment of the underlying disease or disorder that caused CRPS is also important.

To eliminate pain, repeated regional blockades of sympathetic ganglia with local anesthetics are used. When pain is eliminated, vegetative functions are also normalized. Various local anesthetics are also used (for example, ointments, creams and plates with lidocaine). Applications of dimethyl sulfoxide, which has an analgesic effect, have a good effect. A more pronounced analgesic effect is achieved with the application of dimethyl sulfoxide with novocaine. Traditionally, acupuncture, transcutaneous electrical neurostimulation, ultrasound therapy and other types of physiotherapy are used to reduce pain. Hyperbaric oxygenation is effective. Good results are obtained with the appointment of prednisolone (100-120 mg / day) for 2 weeks. Beta-blockers (anaprilin at a dose of 80 mg / day) are used to reduce sympathetic hyperactivity. Calcium channel blockers (nifedipine at a dose of 30-90 mg/day), drugs that improve venous outflow (troxevasin, tribenoside) are also used. Taking into account the pathogenetic role of central pain mechanisms, psychotropic drugs (antidepressants, anticonvulsants - gabapentin, pregabalin) and psychotherapy are recommended. Bisphosphonates are used to treat and prevent osteoporosis.

In conclusion, it should be noted that CRPS remains an insufficiently studied syndrome and the effectiveness of the treatment methods used has yet to be studied in rigorous controlled studies that comply with the principles of evidence-based medicine.